The long term career objectives of this applicant are to obtain an academic position as a basic scientist studying clinically relevant problems. Areas of particular interest include the study of gene regulation as it relates to oncogenesis and hematopoietic differentiation. The faculty of the Washington University Division of Hematology and Oncology have a longstanding record of outstanding and innovative research and a commitment to the development of new investigators. c-fgr is a proto-oncogene belonging to the c-src gene family. It is normally expressed in natural killer cells and terminally differentiated myelomonocytic cells including monocytes, neutrophils and alveolar macrophages. One of the long term objectives of the proposed research is to determine the mechanisms responsible for the tissue- and development- specific regulation of the c-fgr gene. c-fgr is also expressed in Epstein-Barr virus (EBV) infected B-lymphocytes and at least some chronic lymphocytic leukemia (CLL) B-cells, but not in normal or activated B-lymphocytes. Additional long term objectives of the proposed research are to determine the mechanisms and biologic significance of c-fgr gene expression in EBV associated lymphoproliferative disease and CLL. The following specific aims are proposed: 1. We will characterize the cis-acting DNA elements responsible for the tissue- and development- specific expression of the c-fgr gene. 2. We will determine the mechanisms of c-fgr disregulation in EBV infected B-lymphocytes. 3. We will study the regulation and biological significance of c-fgr gene expression in CLL B-cells.